We have improved our sensitivity for the detection of proteins using ESI-quadrupole through optimization of our sample handling procedures and optimization of the instrumental parameters for our commercial Finnigan TSQ-700 triple-quadrupole mass spectrometer. Thus, we have devised a minature desalting catridge that uses packing material that has been carefully optimized for the desalting and recovery of proteins. At the present time, we can obtain high-quality spectra of selected proteins using a 1 pmol loading onto the cartridge. The instrumental parameters have been optimized to the point that we are now able to obtain useful spectra from concentrations of proteins as low as 2 nM.